Liang Weicheng, Lin Zexiao, Du Cong, Qiu Dongbo, Zhang Qi
Vaccine Research Institute, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Mol Cancer. 2020 Feb 26;19(1):38. doi: 10.1186/s12943-020-01166-w.
Despite their small numbers, cancer stem cells play a central role in driving cancer cell growth, chemotherapeutic resistance, and distal metastasis. Previous studies mainly focused on how DNA or histone modification determines cell fate in cancer. However, it is still largely unknown how RNA modifications orchestrate cancer cell fate decisions. More than 170 distinct RNA modifications have been identified in the RNA world, while only a few RNA base modifications have been found in mRNA. Growing evidence indicates that three mRNA modifications, inosine, 5-methylcytosine, and N-methyladenosine, are essential for the regulation of spatiotemporal gene expression during cancer stem cell fate transition. Furthermore, transcriptome-wide mapping has found that the aberrant deposition of mRNA modification, which can disrupt the gene regulatory network and lead to uncontrollable cancer cell growth, is widespread across different cancers. In this review, we try to summarize the recent advances of these three mRNA modifications in maintaining the stemness of cancer stem cells and discuss the underlying molecular mechanisms, which will shed light on the development of novel therapeutic approaches for eradicating cancer stem cells.
尽管癌症干细胞数量较少，但在驱动癌细胞生长、化疗耐药和远处转移方面发挥着核心作用。以往的研究主要集中在DNA或组蛋白修饰如何决定癌症中的细胞命运。然而，RNA修饰如何协调癌细胞命运决定在很大程度上仍不清楚。在RNA世界中已鉴定出170多种不同的RNA修饰，而在mRNA中仅发现了少数几种RNA碱基修饰。越来越多的证据表明，三种mRNA修饰，即肌苷、5-甲基胞嘧啶和N-甲基腺苷，对于癌症干细胞命运转变过程中的时空基因表达调控至关重要。此外，全转录组图谱分析发现，mRNA修饰的异常沉积可破坏基因调控网络并导致癌细胞生长失控，在不同癌症中广泛存在。在本综述中，我们试图总结这三种mRNA修饰在维持癌症干细胞干性方面的最新进展，并讨论其潜在的分子机制，这将为开发根除癌症干细胞的新型治疗方法提供线索。
